Understanding The Development Of Secondary Tumours

Metastasis is a multistep process in which cancer cells grow, become mobile, and disseminate, thereby leading to the development of secondary tumours at a distance from the original tumour. Understanding the mechanisms of metastasis is essential if we are to develop ways to block the formation of secondary tumours. Reporting in the July issue of Nature Cell Biology, Allan Balmain and colleagues at the University of California in San Francisco show that increasing the activation levels of the signalling molecules Smad2 and H-ras sequentially drives tumours through the different stages of becoming metastatic.

The TGF-beta and H-ras signalling pathways had previously been implicated in tumour progression. Now Oft et al. show that activating Smad2, one protein that works with TGF-beta, is sufficient to induce migration of tumour cells. Increasing the amount of H-ras is required, in addition to Smad2 activation, to drive resident epithelial-like cells to develop into mobile fibroblastoid-like cells. A further increase in Smad2 levels in these fibroblastoid-like cancer cells allows them to enter blood vessels and travel to other tissues. These findings have far-reaching implications for preventing secondary-tumour development.